Liquid biopsy to decide the best treatment for NSCLC

In the BFAST analysis, over 2,000 patients with untreated non-small cell lung cancer (NSCLC) had liquid biopsies (blood tests) using state-of-the-art technology to check for multiple driver genetic mutations. Approximately 1 in 20 were found to have tumour DNA showing a rearrangement in the ALK gene. In patients treated with alectinib, a cancer treatment that targets the ALK mutation, over three quarters showed no signs of disease progression in the subsequent 12 months.

New data from the BFAST trial presented by Dr Shirish Gadgeel (University of Michigan, USA) have shown that the test can be used successfully to identify complex DNA mutations in the cells of patients with (NSCLC) suitable for the latest targeted medicines [1]. The sensitive technique detects tumour DNA that is shed from cancer cells into the blood.

In the phase 2/3 BFAST trial, 2,219 patients with stage IIIB/IV untreated NSCLC had blood-based next generation sequencing (NGS) of actionable genetic alterations and results were obtained in 2,188 patients. Overall, 119 patients (5.4%) had ALK+ disease and 87 of these were enrolled to receive alectinib. Median follow-up was 12.6 months. Confirmed objective response rate reported by investigators was 87.4% (95% CI 78.5-93.5) and 12-month duration of response was 75.9% (95% CI 63.6-88.2). Median progression-free survival (PFS) was not reached but 12-month PFS reported by investigators was 78.4% (95% CI 69.1-87.7). Safety data were consistent with the known safety profile of alectinib.

The results are encouraging, as a growing number of patients with advanced lung cancer could be offered a liquid biopsy in complement or instead of tissue biopsy in order to identify their disease mutation and decide the best treatment.

Invited discussant Prof. Alberto Bardelli, (University of Turin, Italy) said: "Rearrangement in the ALK gene described in the BFAST study is typically difficult to detect so it is an important advance to have shown that it can be detected in the blood and used to guide ALK inhibitor treatment, which has then been demonstrated to be effective in patients with this mutation."

1. Gadgeel S et al. ESMO Congress 2019. Abstract LBA81_PR

Posted on 26 November 201918 March 2021